Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis
Lithocholic acid (LCA), alpha-naphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and ethinyl estradiol (EE) are four commonly used chemicals for the construction of acute intrahepatic cholestasis. In order to better understand the mechanisms of acute cholestasis caused...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.907271/full |
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| author | Weiwei Li Weiwei Li Hui Chen Yihan Qian Shouchuan Wang Zichen Luo Jinjun Shan Xiaoni Kong Yueqiu Gao |
| author_facet | Weiwei Li Weiwei Li Hui Chen Yihan Qian Shouchuan Wang Zichen Luo Jinjun Shan Xiaoni Kong Yueqiu Gao |
| author_sort | Weiwei Li |
| collection | DOAJ |
| description | Lithocholic acid (LCA), alpha-naphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and ethinyl estradiol (EE) are four commonly used chemicals for the construction of acute intrahepatic cholestasis. In order to better understand the mechanisms of acute cholestasis caused by these chemicals, the metabolic characteristics of each model were summarized using lipidomics and metabolomics techniques. The results showed that the bile acid profile was altered in all models. The lipid metabolism phenotype of the LCA group was most similar to that of primary biliary cirrhosis (PBC) patients. The ANIT group and the DDC group had similar metabolic disorder characteristics, which were speculated to be related to hepatocyte necrosis and inflammatory pathway activation. The metabolic profile of the EE group was different from other models, suggesting that estrogen-induced cholestasis had its special mechanism. Ceramide and acylcarnitine accumulation was observed in all model groups, indicating that acute cholestasis was closely related to mitochondrial dysfunction. With a deeper understanding of the mechanism of acute intrahepatic cholestasis, this study also provided a reference for the selection of appropriate chemicals for cholestatic liver disease models. |
| first_indexed | 2024-04-12T14:04:48Z |
| format | Article |
| id | doaj.art-e27dfbb634014636b26a337ab6677315 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T14:04:48Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-e27dfbb634014636b26a337ab66773152022-12-22T03:30:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.907271907271Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic CholestasisWeiwei Li0Weiwei Li1Hui Chen2Yihan Qian3Shouchuan Wang4Zichen Luo5Jinjun Shan6Xiaoni Kong7Yueqiu Gao8Department of Formulaology, School of Basic Medicine Science, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCentral Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaJiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaCentral Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaJiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaCentral Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCentral Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaLithocholic acid (LCA), alpha-naphthyl isothiocyanate (ANIT), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and ethinyl estradiol (EE) are four commonly used chemicals for the construction of acute intrahepatic cholestasis. In order to better understand the mechanisms of acute cholestasis caused by these chemicals, the metabolic characteristics of each model were summarized using lipidomics and metabolomics techniques. The results showed that the bile acid profile was altered in all models. The lipid metabolism phenotype of the LCA group was most similar to that of primary biliary cirrhosis (PBC) patients. The ANIT group and the DDC group had similar metabolic disorder characteristics, which were speculated to be related to hepatocyte necrosis and inflammatory pathway activation. The metabolic profile of the EE group was different from other models, suggesting that estrogen-induced cholestasis had its special mechanism. Ceramide and acylcarnitine accumulation was observed in all model groups, indicating that acute cholestasis was closely related to mitochondrial dysfunction. With a deeper understanding of the mechanism of acute intrahepatic cholestasis, this study also provided a reference for the selection of appropriate chemicals for cholestatic liver disease models.https://www.frontiersin.org/articles/10.3389/fphar.2022.907271/fulllipidomicsmetabolomicsacute intrahepatic cholestasismouse modelLC-MSGC-MS |
| spellingShingle | Weiwei Li Weiwei Li Hui Chen Yihan Qian Shouchuan Wang Zichen Luo Jinjun Shan Xiaoni Kong Yueqiu Gao Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis Frontiers in Pharmacology lipidomics metabolomics acute intrahepatic cholestasis mouse model LC-MS GC-MS |
| title | Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis |
| title_full | Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis |
| title_fullStr | Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis |
| title_full_unstemmed | Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis |
| title_short | Integrated Lipidomics and Metabolomics Study of Four Chemically Induced Mouse Models of Acute Intrahepatic Cholestasis |
| title_sort | integrated lipidomics and metabolomics study of four chemically induced mouse models of acute intrahepatic cholestasis |
| topic | lipidomics metabolomics acute intrahepatic cholestasis mouse model LC-MS GC-MS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.907271/full |
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